Significance Bone marrow transplantation in childhood is used to cure a variety of inherited and acquired diseases. For almost all of these conditions, immunosuppressive and marrow ablative chemotherapy is essential to prevent graft rejection, and to "make space" for the donor hematopoietic stem cells (HSC). The need for immunosuppression can be eliminated if the transplant is done in utero when the fetus is in a [unreadable]preimmune[unreadable] state. Objectives In order to overcome the problem of engraftment efficiency and provide an environment that is conducive to in utero HSC transplantation, an understanding of donor cell adhesion and the recipient[unreadable]s hematopoietic environment is essential. Thus, studies focusing on stem cell homing, cell adhesion molecule (CAM) expression and function, and the role cytokines play in these events are under investigation. Results Homing studies were conducted by transplanting early second trimester fetuses with cell preparations which were fluorescently-labeled for tracking purposes. Using flow cytometry, transplanted cells were found in blood, thymus, liver, spleen, and marrow within 24 hours of transplant. Adhesion studies were also conducted using second trimester to neonatal specimens where low density bone marrow mononuclear cells or KG1a cells (human cell line expressing the CD34 antigen) were layered on the surface of frozen liver or bone marrow. Adult marrow cells readily adhered to the later gestation and neonatal livers, whereas no adherance was observed with the early gestation specimens. In contrast, the KG1a cells showed significant adherence to early gestation marrow. These studies suggest that hepatic CAM expression is similar to adult marrow in late gestation, whereas expression differs in early gestation. Future Directions Because differences in CAM expression on fetal liver and/or bone marrow endothelial cells may not be adequate for adult stem cell homing, strategies for overcoming engraftment barriers will be explored. KEYWORDS fetus, hematopoietic ontogeny, stem cell, In Utero transplantation, homing